In biochemical analyses, it is desirable to perform many reactions, sometimes ranging from hundreds to thousands to even tens of thousands, of biological samples in parallel. One way to perform a plurality of reactions in parallel is to use high-density plates or arrays containing many sample wells. High-density microplates are plates, or trays, used for running biological or biochemical tests, with many individually separate sites configured as separate wells per each plate, wherein each well can be used for a separate test. The number of wells on the plates can be 96 wells, 384 wells, 864 wells, 1536 wells or more. The plates may also have no physically separate wells, in which case, the plates can be flat plates with discrete or indiscrete deposit sites.
In other applications such as digital polymerase chain reactions (PCR), the sample assay is partitioned into sub-reactions. One effective way to do that is to use a high-density array comprising thousands of open-ended sample wells. Typically, the wells are packed very close together. The dividing wall between adjacent wells can have a thickness ranging from 1 μm to 100 μm.
In general, after the wells have been filled with respective sample assays, the assays are sealed within the wells using a compatible immiscible liquid, such as mineral oil. Normally, that would be sufficient to isolate the reactions in the sample assays and prevent them from interacting with one another. However, when the array is subjected to heating, such as in a thermal cycling process common in PCR, sealing by a mineral oil layer may be ineffective in isolating the assays in the respective wells. For example, heating might cause the assays to expand out of the wells, and thus create contact between adjacent assays. The presence of air gaps, particularly at the oil-assay interface, may exacerbate the problem, since air expands faster when heated and may then push the assay out of the well. If the surfaces of the array are hydrophilic, there is also a higher tendency for the assays to flow out of the respective wells when heated. Any liquid not capped with the mineral oil layer may easily exit a micro-capillary, spill over onto an open end of an adjacent well and be drawn into the adjacent well.
It is desirable for the individual assays in the high-density array to be discrete and isolated from one another, particularly during a heating process where there is a strong tendency for assays to expand and interact with adjacent assays. When the assays are allowed to physically contact one another during a biochemical process, erroneous results such as false positives may occur.
Cross-contamination of samples can be prevented by increasing the separation between adjacent samples. In current techniques, wells are pre-fabricated so that there is sufficient spacing between them. However, such arrays have reduced well densities.
Thus, there is a need to provide a method and device for isolating liquid samples that overcome, or at least ameliorate, one or more of the disadvantages described above.